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Title: Absence of association between Plasmodium falciparum small sub-unit ribosomal RNA gene mutations and in vitro decreased susceptibility to doxycycline
Authors: Tiphaine Gaillard
Nathalie Wurtz
Sandrine Houzé
Kanlaya Sriprawat
Chirapat Wangsing
Véronique Hubert
Jacques Lebras
François Nosten
Sébastien Briolant
Bruno Pradines
Institut de recherche biomedicale des armees
Unite de Recherche sur les Maladies Infectieuses et Tropicales emergentes
HIA Sainte-Anne a Toulon
Centre National de Référence du Paludisme
Hopital Bichat-Claude-Bernard AP-HP
IRD Institut de Recherche pour le Developpement
Universite Paris Descartes
Mahidol University
University of Oxford
Institut Pasteur de la Guyane
Keywords: Immunology and Microbiology;Medicine
Issue Date: 17-Sep-2015
Citation: Malaria Journal. Vol.14, No.1 (2015)
Abstract: © 2015 Gaillard et al. Background: Doxycycline is an antibiotic used in combination with quinine or artesunate for malaria treatment or alone for malaria chemoprophylaxis. Recently, one prophylactic failure has been reported, and several studies have highlighted in vitro doxycycline decreased susceptibility in Plasmodium falciparum isolates from different areas. The genetic markers that contribute to detecting and monitoring the susceptibility of P. falciparum to doxycycline, the pfmdt and pftetQ genes, have recently been identified. However, these markers are not sufficient to explain in vitro decreased susceptibility of P. falciparum to doxycycline. In this paper, the association between polymorphism of the small sub-unit ribosomal RNA apicoplastic gene pfssrRNA (PFC10-API0057) and in vitro susceptibilities of P. falciparum isolates to doxycycline were investigated. Methods: Doxycycline IC<inf>50</inf> determinations using the hypoxanthine uptake inhibition assay were performed on 178 African and Thai P. falciparum isolates. The polymorphism of pfssrRNA was investigated in these samples by standard PCR followed by sequencing. Results: No point mutations were found in pfssrRNA in the Thai or African isolates, regardless of the determined IC<inf>50</inf> values. Conclusions: The pfssrRNA gene is not associated with in vitro decreased susceptibility of P. falciparum to doxycycline. Identifying new in vitro molecular markers associated with reduced susceptibility is needed, to survey the emergence of doxycycline resistance.
ISSN: 14752875
Appears in Collections:Scopus 2011-2015

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